Model‐based analysis of the sensitivities and diagnostic implications of FFR and CFR under various pathological conditions

Abstract

Although fractional flow reserve (FFR) and coronary flow reserve (CFR) are both frequently used to assess the functional severity of coronary artery stenosis, discordant results of diagnosis between FFR and CFR in some patient cohorts have been reported. In the present study, a computational model was employed to quantify the impacts of various pathophysiological factors on FFR and CFR. In addition, a hyperemic myocardial ischemic index (HMIx) was proposed as a reference for comparing the diagnostic performances of FFR and CFR. Obtained results showed that CFR was more susceptible than FFR to the influence of many pathophysiological factors unrelated to coronary artery stenosis. In particular, the numerical study proved that increasing hyperemic coronary microvascular resistance significantly elevated FFR while reducing CFR despite fixed severity of coronary artery stenosis, whereas introducing aortic valve disease only caused a significant decrease in CFR with little influence on FFR. These results provided theoretical evidence for explaining some clinical observations, such as the increased risk of discordant diagnostic results between FFR and CFR in patients with increased hyperemic microvascular resistance, and significant increase in CFR after surgical relief of severe aortic valve disease. When evaluated with respect to the predictive value for hyperemic myocardial ischemia, the performance of FFR was found to be considerably compromised in the presence of severe coronary vasodilation dysfunction or aortic valve disease, whereas the relationship between CFR and HMIx remained relatively stable, suggesting that CFR may be a more reliable indicator of myocardial ischemia under complex pathophysiological conditions.

Comparison of Instantaneous Wave-Free Ratio (iFR) and Fractional Flow Reserve (FFR) with respect to Their Sensitivities to Cardiovascular Factors: A Computational Model-Based Study

“…e computational model was adapted from the models developed in our previous studies [21,22] where the modeling methods and associated numerical schemes have been described in detail. In brief, a zero-one-dimensional (0-1-D) multiscale modeling method was employed to represent the coronary circulation coupled to the global cardiovascular system.…”

“…Comparisons of model predictions and in vivo measurements under resting and hyperemic conditions are summarized in Table 1. In cases when aortic valve diseases (e.g., stenosis and regurgitation) were present, model parameters such as resting intramyocardial vascular resistance and systemic vascular resistance were further adjusted so that model-predicted coronary arterial flow and systemic arterial pressure were comparable to those measured in patients with aortic valve disease [25,26] (refer to [21] for more details).…”

“…Under the resting condition, although the presence of severe AS induced a marked decrease in both aortic and poststenosis coronary pressures, the degree of decrease in poststenosis pressure was larger than that of aortic pressure, resulting in an evident decrease in iFR. e enhanced decrease in poststenosis pressure was caused mainly by the increased resting coronary blood flow (which augments the pressure drop across the stenosis) as a consequence of coronary microvascular adaptive responses to increased myocardial stress and oxygen demand in the presence of AS [21]. Under the hyperemic condition, the simulated coronary blood flow rate in the presence of AS was however comparable to or even slightly lower than that under the control condition (which is consistent with previous clinical observations [44]), leading to a mild increase in FFR.…”

“…All clinical data used in the present study have been reported in the corresponding references and the values of most model parameters not provided in the manuscript have been reported in a previous study of ours [21] (https:// onlinelibrary.wiley.com/doi/full/10.1002/cnm.3257).…”

“…A stenosis was introduced in the middle segment of LAD, with blood pressure immediately distal to it (P d ) being monitored along with blood pressure at the aortic root (P a ) for the purpose of calculating iFR or FFR. More details of model development, parameter assignment, and numerical methods have been described in our previous studies[21,22]. Abbreviations: LM, left main artery; LAD, left anterior descending coronary artery; LCx, left circumflex coronary artery; RCA, right coronary artery.…”